The questionable approval of aducanumab and the recent approval of lecanemab (Leqembi; Eisai and Biogen) by the FDA has raised the issue of safety (stroke, meningitis, and encephalitis) over efficacy (slowing of cognitive decline). This communication recounts the important physiological functions of amyloid-β as a barrier protein with unique sealant and anti-pathogenic activities important for maintaining vascular integrity coupled with innate immune functions that prevent encephalitis and meningitis. The approval of a drug that obviates both of these purposive functions increases the risk of hemorrhage, edema and downstream pathogenic outcomes and should be clearly outlined to patients.
Keywords: ARIA; Adverse events; amyloid-β; cognition; edema; hemorrhage; innate immunity; lecanemab; pathogen; stroke.